Role of toll-like receptor 7 (TLR7) in voluntary alcohol consumption.

Brain, Behavior, and Immunity
E K GranthamR A Harris

Abstract

Overactivation of neuroimmune signaling has been linked to excessive ethanol consumption. Toll-like receptors (TLRs) are a major component of innate immune signaling and initiate anti- and pro-inflammatory responses via intracellular signal transduction cascades. TLR7 is upregulated in post-mortem brain tissue from humans with alcohol use disorder (AUD) and animals with prior exposure to ethanol. Despite this evidence, the role of TLR7 in the regulation of voluntary ethanol consumption has not been studied. We test the hypothesis that TLR7 activation regulates voluntary ethanol drinking behavior by administering a TLR7 agonist (R848) during an intermittent access drinking procedure in mice. Acute activation of TLR7 reduced ethanol intake, preference, and total fluid intake due, at least in part, to an acute sickness response. However, chronic pre-treatment with R848 resulted in tolerance to the adverse effects of the drug and a subsequent increase in ethanol consumption. To determine the molecular machinery that mediates these behavioral changes, we evaluated gene expression after acute and chronic TLR7 activation. We found that acute TLR7 activation produces brain region specific changes in expression of immune pathway genes, ...Continue Reading

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Citations

Feb 22, 2021·Journal of Neuroscience Research·Fulton T CrewsLeon G Coleman
Mar 16, 2021·Bioscience Trends·Marat AirapetovPetr Shabanov
Apr 4, 2021·International Journal of Molecular Sciences·Liya QinLeon G Coleman
Jul 19, 2021·Biological Psychiatry·Robert HitzemannTamara J Phillips
Jul 25, 2021·International Journal of Molecular Sciences·Javier Calleja-CondeJose Antonio López-Moreno

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